Figure 1.

[Ca²⁺]_i homeostasis regulation in precapillary pulmonary arterial smooth muscle cells (PASMCs) and ECs. Ca²⁺ enters cells from extracellular fluid through L-type voltage-dependent calcium channels or non-selective cation channels, which can be divided into SOCCs and ROCCs. The initiation of ROCC-mediated Ca²⁺-influx from the extracellular space is thought to be induced by ligand-activated G-protein coupled receptors, starting a PLC-mediated hydrolyzation of PIP₂ to IP₃ and DAG. DAG regulates the activity of ROCC to induce receptor-operated Ca²⁺ entry, whereas IP₃ generation induces depletion of the intracellular Ca²⁺ stores in the endoplasmic reticulum, leading to induction of store-operated Ca²⁺ entry. The increased [Ca²⁺]_i drives different cellular responses. Ca²⁺, calcium ion; [Ca²⁺]_i, intracellular Ca²⁺ concentration; ROCC, receptor-operated calcium channel; SOCC, store-operated calcium channel; VDCC, L-type voltage-dependent calcium channel; DAG, diacylglycerol; DAGK, DAG kinase; EC, endothelial cell; ER/SR, endoplasmic/sarcoplasmic reticulum; IP₃, inositol trisphosphate; IP₃R, inositol trisphosphate receptor; L, ligand; PA, phosphatidic acid; PASMC, precapillary pulmonary arterial smooth muscle cells; PIP₂, phosphatidylinositol 4,5-bisphosphate; PLC, phospholipase C; VEGF, vascular endothelial growth factor; solid arrows indicate direct interactions; dotted arrows illustrate indirect interactions.